Salivary Citrate Deficiency Defines an Endogenous Dentin Remineralization Failure State Through Glandular MT1/2-Zn²⁺-ACO2 Dysregulation.
4 affiliations
- 1Department of Operative Dentistry and Endodontics, the Affiliated Stomatological Hospital of Nanjing Medical University and School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
- 2Department of Prosthodontics, the Affiliated Stomatological Hospital of Nanjing Medical University and School of Stomatology, Nanjing Medical University, Nanjing, Jiangsu, People's Republic of China.
- 3Department of Endodontics, The Dental College of Georgia, Augusta University, Augusta, Georgia, USA.
- 4Department of Stomatology, Nanjing First Hospital, Nanjing, Jiangsu, People's Republic of China.
Abstract
Rapid caries progression occurs even when salivary flow and calcium phosphate availability are preserved, suggesting a knowledge gap in how available minerals are used for repair. Early-stage Sjögren's syndrome was examined as a clinical model of this condition. Salivary citrate was markedly lower in the disease cohort and was inversely associated with caries burden, whereas salivary flow and the major mineral ions did not differ from healthy controls. In mineralization systems with matched calcium and phosphate concentrations, the disease-associated citrate concentration reduced intrafibrillar mineral deposition, disrupted hydroxyapatite organization, and limited structural and mechanical recovery of demineralized dentin. Human salivary gland tissue, an immunization-induced rat model, and primary salivary gland epithelial cells showed a similar metabolic pattern: increased metallothionein 1/2 (MT1/2), reduced labile Zn²⁺, increased aconitase 2 (ACO2) activity, and citrate depletion. ZnSO₄ repletion increased intracellular Zn²⁺, reduced ACO2 activity, restored citrate toward control levels, and improved the mineralization activity of epithelial-cell supernatants. The data indicate that citrate availability influences dentin mineral utilization and associate citrate depletion with glandular MT1/2-Zn²⁺-ACO2 dysregulation. These findings support an association between glandular zinc-citrate dysregulation and impaired remineralization, suggesting that this mechanism may account for impaired endogenous remineralization despite preserved availability of the major mineral ions.
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BibTeX
@article{you2026salivary,
title = {{Salivary Citrate Deficiency Defines an Endogenous Dentin Remineralization Failure State Through Glandular MT1/2-Zn²⁺-ACO2 Dysregulation.}},
author = {Ran You and Wenhui Wang and Franklin R Tay and Haotian Dong and Mutong Wei and Ruoyun Wu and Xin Song and Chen Chen and Haifeng Xie},
journal = {Advanced science (Weinheim, Baden-Wurttemberg, Germany)},
year = {2026},
month = oct,
doi = {10.1002/advs.78578},
url = {https://europepmc.org/article/MED/42958706},
note = {CC BY},
}
RIS
TY - JOUR
TI - Salivary Citrate Deficiency Defines an Endogenous Dentin Remineralization Failure State Through Glandular MT1/2-Zn²⁺-ACO2 Dysregulation.
AU - Ran You
AU - Wenhui Wang
AU - Franklin R Tay
AU - Haotian Dong
AU - Mutong Wei
AU - Ruoyun Wu
AU - Xin Song
AU - Chen Chen
AU - Haifeng Xie
PY - 2026
DA - 2026/10/29
JO - Advanced science (Weinheim, Baden-Wurttemberg, Germany)
DO - 10.1002/advs.78578
UR - https://europepmc.org/article/MED/42958706
AB - Rapid caries progression occurs even when salivary flow and calcium phosphate availability are preserved, suggesting a knowledge gap in how available minerals are used for repair. Early-stage Sjögren's syndrome was examined as a clinical model of this condition. Salivary citrate was markedly lower in the disease cohort and was inversely associated with caries burden, whereas salivary flow and the major mineral ions did not differ from healthy controls. In mineralization systems with matched calcium and phosphate concentrations, the disease-associated citrate concentration reduced intrafibrillar mineral deposition, disrupted hydroxyapatite organization, and limited structural and mechanical recovery of demineralized dentin. Human salivary gland tissue, an immunization-induced rat model, and primary salivary gland epithelial cells showed a similar metabolic pattern: increased metallothionein 1/2 (MT1/2), reduced labile Zn²⁺, increased aconitase 2 (ACO2) activity, and citrate depletion. ZnSO₄ repletion increased intracellular Zn²⁺, reduced ACO2 activity, restored citrate toward control levels, and improved the mineralization activity of epithelial-cell supernatants. The data indicate that citrate availability influences dentin mineral utilization and associate citrate depletion with glandular MT1/2-Zn²⁺-ACO2 dysregulation. These findings support an association between glandular zinc-citrate dysregulation and impaired remineralization, suggesting that this mechanism may account for impaired endogenous remineralization despite preserved availability of the major mineral ions.
SN - 2198-3844
ER -